The clinical, epidemiological and experimental evidence presently available suggests that ovarian steroids directly influence normal melanocyte and melanoma cell functions. The mechanism(s) underlying their action remains to be resolved. We have recently suggested that estrogen and progesterone alter melanocyte proliferation and melanogenesis via specific, high affinity receptors in a manner similar to the action of these steroids in other target tissues. The objectives of this research are: (1)\to expand the applicant's initial observations; (2)\to determine whether the biological response of normal melanocytes to estrogen, is mediated via cytosol receptor translocation to the nucleus in a manner similar to melanoma cells. (These studies are critical in determing whether melanoma cells reflect and magnify the receptor status and estrogen responsiveness of normal melanocytes.); and (3)\to answer the question of whether estrogen-\and progesterone-induced alterations of melanocyte proliferation and melanogenesis take place via receptor activation of transcriptional events or by a direct post-translational effect on enzyme function. (The induction of two marker enzymes for growth and melanogenesis, ornithine decarboxylase (ODC) and tyrosinase, respectively, will be followed.) We have developed a panel of well-characterized culture systems of human melanoma cells as well as human and guinea pig melanocytes as probes to study estrogen's action. We have identified and quantified cytosol and nuclear receptors for estradiol in human melanoma cells and from histologically normal human melanocytes (nevi). In addition to its heuristic value in determining how ovarian steroids influence mammalian melanocyte proliferation and melanogenesis, it is expected that this new basic information on how estradiol and progesterone affect melanocyte and melanoma function will provide a better estimate of the role of ovarian steroids in the natural history of human melanoma and improve clinical management of this lesion.